Resonance in the nonadiabatic quantum pumping of the time-dependent Josephson junction

In this work, we investigated the nonadiabatic transport properties of the one-dimensional time-dependent superconductor-normal metal-superconductor (SNS) Josephson junction biased by a current source and driven by a high-frequency-ac-gate-potential applied to the normal-metal layer. BCS superconductors are considered and treated with the time-dependent Bogoliubov-de Gennes equation. Using Floquet theory, we compute the transmission coefficients and the Wigner-Smith delay times as a function of the incident energy and find that they display resonances when one of the electron or hole Floquet wavevectors coincides with the bound quasiparticle state within the superconducting energy gap. The resonance varies with the phase difference between the two superconductors as a result of the bound quasiparticle level displacement. The supercurrent flowing through the SNS junction is dramatically enhanced by the resonances

Strategic Asset Seeking and Innovation Performance: The Role of Innovation Capabilities and Host Country Institutions

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Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.

The endoplasmic reticulum (ER)-anchored hepatic cytochromes P450 (P450s) are enzymes that metabolize endo- and xenobiotics i.e. drugs, carcinogens, toxins, natural and chemical products. These agents modulate liver P450 content through increased synthesis or reduction via inactivation and/or proteolytic degradation, resulting in clinically significant drug-drug interactions. P450 proteolytic degradation occurs via ER-associated degradation (ERAD) involving either of two distinct routes: Ubiquitin (Ub)-dependent 26S proteasomal degradation (ERAD/UPD) or autophagic lysosomal degradation (ERAD/ALD). CYP3A4, the major human liver/intestinal P450, and the fast-turnover CYP2E1 species are degraded via ERAD/UPD entailing multisite protein phosphorylation and subsequent ubiquitination by gp78 and CHIP E3 Ub-ligases. We are gaining insight into the nature of the structural determinants involved in CYP3A4 and CYP2E1 molecular recognition in ERAD/UPD [i.e. K48-linked polyUb chains and linear and/or "conformational" phosphodegrons consisting either of consecutive sequences on surface loops and/or disordered regions, or structurally-assembled surface clusters of negatively charged acidic (Asp/Glu) and phosphorylated (Ser/Thr) residues, within or vicinal to which, Lys-residues are targeted for ubiquitination]. Structural inspection of select human liver P450s reveals that such linear or conformational phosphodegrons may indeed be a common P450-ERAD/UPD feature. By contrast, although many P450s such as the slow-turnover CYP2E1 species and rat liver CYP2B1 and CYP2C11 are degraded via ERAD/ALD, little is known about the mechanism of their ALD-targeting. On the basis of our current knowledge of ALD-substrate targeting, we propose a tripartite conjunction of K63-linked Ub-chains, P450 structural "LIR" motifs and selective cellular "cargo receptors" as plausible P450-ALD determinants